Lymphotoxin

Abstract

LT was one of the first lymphokines to be described and has been one of the most difficult to fit into a conceptual framework. Now, 20 years after its discovery, its structure, genetic organization, and linkage are well understood in mouse and human, and insight has been gained into its biological role. It is a T cell-derived glycoprotein of 25 kd coded by a gene within the MHC. It is somewhat (35%) structurally homologous to the macrophage product TNF. The genes for LT and TNF are tightly linked, and the proteins share most biological activities and compete for the same cell surface receptor. LT is induced in an antigen-specific MHC restricted fashion from class I and class II restricted T cells. Viral infection is also associated with LT production by lymphoid cells. LT has several effects on target cells including killing, growth stimulation, and induction of differentiation. The mechanism of LT's effects involves receptor binding and internalization and several sequelae including changes in prostaglandins and chromosome integrity. LT probably plays several biological roles. It can contribute to immunoregulation, defense against viruses, parasitic infections, and rejection of tumors. Understanding LT's role in the pathogenesis of diseases of autoimmunity and immune dysregulation will be the key to devising effective regimens for prophylaxis and treatment.